Deep Molecular Characterization of Milder Spinal Muscular Atrophy Patients Carrying the c.859G>C Variant in SMN2

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by biallelic loss or pathogenic variants in the SMN1 gene. Copy number and modifier intragenic variants in SMN2, an almost identical paralog gene of SMN1, are known to influence the amount of complete SMN proteins. Therefore, SMN2 is considered the main phenotypic modifier of SMA, although genotype-phenotype correlation is not absolute. We present eleven unrelated SMA patients with milder phenotypes carrying the c.859G>C-positive modifier variant in SMN2. All were studied by a specific NGS method to allow a deep characterization of the entire SMN region. Analysis of two homozygous cases for the variant allowed us to identify a specific haplotype, Smn2-859C.1, in association with c.859G>C. Two other cases with the c.859G>C variant in their two SMN2 copies showed a second haplotype, Smn2-859C.2, in cis with Smn2-859C.1, assembling a more complex allele. We also identified a previously unreported variant in intron 2a exclusively linked to the Smn2-859C.1 haplotype (c.154-1141G>A), further suggesting that this region has been ancestrally conserved. The deep molecular characterization of SMN2 in our cohort highlights the importance of testing c.859G>C, as well as accurately assessing the SMN2 region in SMA patients to gain insight into the complex genotype-phenotype correlations and improve prognostic outcomes

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Using a modified Delphi methodology to gain consensus on the use of dressings in chronic wounds management

Objective: Managing chronic wounds is associated with a burden to patients, caregivers, health services and society and there is a lack of clarity regarding the role of dressings in improving outcomes. This study aimed to provide understanding on a range of topics, including: the definition of chronicity in wounds, the burden of illness, clinical outcomes of reducing healing time and the impact of early interventions on clinical and economic outcomes and the role of matrix metalloproteinases (MMPs) in wound healing. Method: A systematic review of the literature was carried out on the role of dressings in diabetic foot ulcer (DFU), and venous leg ulcer (VLU) management strategies, their effectiveness, associated resource use/cost, and quality of life (QoL) impact on patients. From this evidence-base statements were written regarding chronicity in wounds, burden of illness, healing time, and the role of MMPs, early interventions and dressings. A modified Delphi methodology involving two iterations of email questionnaires followed by a face-to-face meeting was used to validate the statements, in order to arrive at a consensus for each. Clinical experts were selected, representing nurses, surgeons, podiatrists, academics, and policy experts. Results: In the first round, 38/47 statements reached or exceeded the consensus threshold of 80% and none were rejected. According to the protocol, any statement not confirmed or rejected had to be modified using the comments from participants and resubmitted. In the second round, 5/9 remaining statements were confirmed and none rejected, leaving 4 to discuss at the meeting. All final statements were confirmed with at least 80% consensus. Conclusion: This modified Delphi panel sought to gain clarity from clinical experts surrounding the use of dressings in the management of chronic wounds. A full consensus statement was developed to help clinicians and policy makers improve the management of patients with these conditions

Long-term cognitive and functional status in survivors of an aneurysmal subarachnoid hemorrhage: Analysis of a retrospective cohort

Data de publicació electrònica: 13-04-2021Objetivo: Existe poca información sobre los resultados funcionales y cognitivos a largo plazo en pacientes con hemorragia subaracnoidea aneurismática (HSA). El objetivo principal fue evaluar la situación cognitiva, funcional, anímica y la calidad de vida en personas con HSA a largo plazo. Pacientes y método: Estudio de corte transversal de una cohorte de 40 pacientes (edad media 58,2 [DE 9,9] años) con HSA ingresados en la unidad de Rehabilitación neurológica entre enero del 2010 a julio del 2017. Variables de resultado: estado cognitivo (cuestionario de Pfeiffer), nivel funcional (índice de Barthel), depresión (escala de Hamilton) y calidad de vida (European Quality of Life-5 Dimensions [EQ-5D]), así como las terapias de rehabilitación realizadas en un seguimiento mínimo de seis meses post-HSA. Resultados: De 35 pacientes con alteraciones cognitivas en fase aguda, solo 12 realizaron terapia cognitiva tras el alta hospitalaria. En el seguimiento a largo plazo, los déficits cognitivos persistían en 22 casos, y en comparación con el resto, presentaban peores puntuaciones en el índice de Barthel (15,5 [IC 95% 1,2 a 29,7]), la escala de Hamilton (-0,8 [IC 95% -1,27 a -0,37]), y la EQ-5D (27,6 [IC 95% 12,4 a 19]). Conclusión: La prevalencia de déficits cognitivos a largo plazo en supervivientes de una HSA es alta y su presencia se relaciona con un peor estado funcional, más depresión y peor calidad de vida. El bajo porcentaje de individuos que realizan terapia cognitiva en su proceso de rehabilitación junto con las repercusiones clínicas observadas apoyan la necesidad de incluir las terapias neurocognitivas en los programas de rehabilitación de las HSA.Objective: Little data is available on long-term functional and cognitive outcomes in patients with aneurysmal subarachnoid hemorrhage (ASH). The main objective of this study was to assess cognition, functional state, mood disorders, and quality of life in patients with SAH at least six months following the ASH. Patients and methods: Cross-sectional study of 40 patients (aged 58.2 [SD 9.9] years) with ASH, discharged from a Neurologic Rehabilitation unit between January 2010 and July 2017. Main outcome variables: functional status (Barthel index), cognition (Pfeiffer questionnaire), depression (Hamilton scale), and health-related quality of life (European Quality of Life-5 Dimensions [EQ-5D]), as well as type and duration of therapeutic rehabilitation procedures after discharge. Results: From 35 patients with cognitive disorders, only 12 received cognitive therapy at hospital discharge. In the long-term follow-up, cognitive impairment persisted in 22 patients. When compared with those without cognitive impairment, they presented significantly worse mean differences in the Barthel index (15.5 [95% CI: 1.2-29.7]), Hamilton scale (-0.8 [95% CI: -1.27 to -0.37]), and EQ-5D (27.6 [95% CI: 12.4-19]). Conclusion: The prevalence of long-term cognitive impairments in survivors of a SAH episode is high, and their presence is associated with worse functional status, more depression and worse quality of life. The low percentage of subjects who received cognitive therapies through their recovery process and the clinical implications observed, support the need of including neuropsychological therapies in the rehabilitation programs after an SAH event

Effects of prophylactic swallowing exercises on dysphagia and quality of life in patients with head and neck cancer receiving (chemo) radiotherapy: the Redyor study, a protocol for a randomized clinical trial

Background: Radiation-induced dysphagia is common in patients with head and neck cancer (HNC). Available evidence suggests that exercise therapy prior to oncological treatment could potentially improve deglutition and quality of life; however, a randomized clinical trial is needed to confirm this observation. Methods/design: The Redyor study is a single-blind randomized clinical trial designed to compare the effect of prophylactic oropharyngeal exercises on quality of life and dysphagia of 52 patients with HNC referred to the Radiotherapy Department. The intervention will consist of respiratory muscle training (3 times/day, 5 days/week, 21 weeks) added to the standard swallow therapy. All patients will perform the same exercise intervention, but at different times: before chemoradiotherapy (CRT; early intervention group) or immediately after completing CRT (late intervention group). The main outcome will be change in dysphagia severity assessed with the Penetration-Aspiration Scale in videofluoroscopy study; quality of life will be assessed with the EORTC-QLQ-C30 and its Head and Neck Cancer Module (QLQ-H&N35) at 3, 6, and 12 months after completing CRT. Discussion: This ongoing clinical trial, registered in 2016, is based on the hypothesis that undergoing a pre-radiotherapy rehabilitation (pre-habilitation) program will have greater benefits (less decrease in quality of life, less delay in swallowing parameters, and less severe dysphagia) compared to post-CRT rehabilitation. The main objective is to assess dysphagia severity in HNC patients; and secondly, to evaluate changes in dysphagia-related quality of life, and to determine the correlation between a clinical variable and instrumental parameters during this period